ticarcillin/clavulanate (Rx)

1-10%

Rash

Nausea

Diarrhea

Phlebitis at injection site

Increased eosinophils

Increased AST

Increased ALT

Postmarketing Reports

Hypersensitivity reactions: Skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, chest discomfort, anaphylactic reactions, and bullous reactions (including erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome)

CNS: Headache, giddiness, neuromuscular hyperirritability, or convulsive seizures

Gastrointestinal: Disturbances of taste and smell, stomatitis, flatulence, nausea, vomiting and diarrhea, epigastric pain, and pseudomembranous colitis have been reported; onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment

Hemic and lymphatic systems: Thrombocytopenia, leukopenia, neutropenia, eosinophilia, reduction of hemoglobin or hematocrit, and prolongation of prothrombin time and bleeding time

Hepatic function tests: Elevation of AST, ALT, serum alkaline phosphatase, serum LDH, and serum bilirubin; transient hepatitis and cholestatic jaundice reported

Renal: Hemorrhagic cystitis, elevation of serum creatinine and/or BUN, hypernatremia, reduction in serum potassium, and uric acid

Local reactions: Pain, burning, swelling, and induration at the injection site, and thrombophlebitis with IV administration

Contraindications

Allergy to penicillins or other beta-lactam antibacterials (eg, cephalosporins, imipenem)

Cautions

Serious and occasionally fatal hypersensitivity reactions reported

Clostridium difficile associated diarrhea reported with use of nearly all antibacterial agents, including ticarcillin

Seizures reported when dose exceeded, especially in presence of renal impairment

Risk of bleeding complication

Potential for microbial overgrowth or bacterial resistance

Laboratory tests: High urine concentrations of ticarcillin may produce false-positive protein reactions; clavulanate may cause a nonspecific binding of IgG and albumin by RBC leading to a false-positive Coombs test

Hypokalemia reported

Monitor renal, hepatic, and hematologic function

Mechanism of Action

Inhibits cell wall biosynthesis by binding to 1 of more penicillin binding proteins, which subsequently inhibits bacterial cell wall synthesis and has a bactericidal effect

Absorption

Absorption: 86% (IM)

Peak Plasma Time: 30-75 min (IM)

Peak Plasma Concentration: 324 mcg/mL (immediately after 30 min IV infusion of 3.1 g)

AUC: 485 mcg•hr/mL (ticarcillin); 8.2 mcg•hr/mL (clavulanic acid)

Distribution

Protein Bound: 45 (ticarcillin); 25% (Clavulanate)

Distributed into bile, low concentrations in CSF

Metabolism

Liver

Elimination

Half-life: 1.1 hr adults; 4.4 hr neonates; 1 hr infants/children

Excretion: 60-70% urine (ticarcillin), 35-45% (clavulainic acid), excreted unchanged in first 6 hr after administration

IV Incompatibilities

Additive: sodium bicarbonate, aminoglycosides, ciprofloxacin(?)

Y-site: alatrofloxacin, amphotericin B cholesteryl sulfate, azithromycin, cisatracurium(?), topotecan(?), vancomycin(?)

IV Compatibilities

Solution: compatible w/ most common solvents

Y-site: (partial list) allopurinol, clarithromycin, diltiazem, fluconazole, heparin, meperidine, morphine, ondansetron, propofol

IV Preparation

Reconstitute 3.1 g vial with 13 mL SWI or NS; final concentration 200 mg/6.7 mg/mL

For intermittent IV infusion, further dilute to 10-100 mg/mL (ticarcillin component with compatible IV solution

IV Administration

Intermittent IV infusion over 30 min

Administer 1 hr apart from aminoglycosides

Storage

Reconstituted solution is stable for 6 hr at room temperature and 72 hr when refrigerated

IV infusion in NS is stable for 24 hr at room temperature and 7 days when refrigerated, or 30 days when frozen

Darkening indicates loss of potency